ArticleBreast cancer research : BCR2024
Association of early menarche with breast tumor molecular features and recurrence.
Article in Breast cancer research : BCR, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers, 1 of them a synthesis that pooled it.
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Who cites it
13 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Allostatic load in female cancer patients: a systematic review.Frontiers in endocrinology · 2026Pooled it
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- Reproductive Fitness and the Links to Chronic Disease and Systemic Aging.Physiology (Bethesda, Md.) · 2026Review
- Breast Cancer Molecular Subtypes and Receptor-Related Risk Factor Associations: A Cross-Sectional Study.Health science reports · 2026Article
- Development and validation of a nomogram for predicting axillary reverse mapping lymph node metastasis in breast cancer patients.Frontiers in oncology · 2026Article
- Secular trends in age at menarche among Han Chinese females in Shanghai: a large-scale community-based study.BMC women's health · 2025Article
- Early thelarche, reproductive hormones, and MRI-based breast density: a prospective study in China.Breast cancer research : BCR · 2025Article
- Associations of area-level and individual-level sociodemographic factors with adolescent phenotypes linked to subsequent cancer risk.Reproductive toxicology (Elmsford, N.Y.) · 2025Article
- Control of epithelial homeostasis by apical polarity: it takes a network.Biochemical Society transactions · 2025Article
- Identification and modulation of a PI3K/AKT/mTOR pathway-targeting microRNA in order to increase colorectal cancer cells radiosensitivity in vitro.BMC cancer · 2025Article
- The impact of reproductive factors on breast tumor and normal-adjacent tissue immune profile from menarche to menopause.Carcinogenesis · 2025Article
- Comprehensive Analysis of Predictors and Outcomes in Breast Cancer Screening in Romania: Insights from Demographic, Clinical, and Lifestyle Factors.Journal of clinical medicine · 2025Article
- Inflammatory factors collaboratively linkFrontiers in immunology · 2025Review
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17 authors.
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Abstract
backgroundEarly menarche is an established risk factor for breast cancer but its molecular contribution to tumor biology and prognosis remains unclear.
methodsWe profiled transcriptome-wide gene expression in breast tumors (N = 846) and tumor-adjacent normal tissues (N = 666) from women in the Nurses' Health Studies (NHS) to investigate whether early menarche (age < 12) is associated with tumor molecular and prognostic features in women with breast cancer. Multivariable linear regression and pathway analyses using competitive gene set enrichment analysis were conducted in both tumor and adjacent-normal tissue and externally validated in TCGA (N = 116). Subgroup analyses stratified on ER-status based on the tumor were also performed. PAM50 signatures were used for tumor molecular subtyping and to generate proliferation and risk of recurrence scores. We created a gene expression score using LASSO regression to capture early menarche based on 28 genes from FDR-significant pathways in breast tumor tissue in NHS and tested its association with 10-year disease-free survival in both NHS (N = 836) and METABRIC (N = 952).
resultsEarly menarche was significantly associated with 369 individual genes in adjacent-normal tissues implicated in extracellular matrix, cell adhesion, and invasion (FDR ≤ 0.1). Early menarche was associated with upregulation of cancer hallmark pathways (18 significant pathways in tumor, 23 in tumor-adjacent normal, FDR ≤ 0.1) related to proliferation (e.g. Myc, PI3K/AKT/mTOR, cell cycle), oxidative stress (e.g. oxidative phosphorylation, unfolded protein response), and inflammation (e.g. pro-inflammatory cytokines IFN
conclusionsEarly menarche is associated with more aggressive molecular tumor characteristics and its gene expression signature within tumors is associated with worse 10-year disease-free survival among women with breast cancer. As the age of onset of menarche continues to decline, understanding its relationship to breast tumor characteristics and prognosis may lead to novel secondary prevention strategies.
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